Pneumonia can be caused by a variety of pathogenic organisms including bacteria, fungi and viruses and is the leading cause of death worldwide. Even in developed countries, pneumonia continues to be the leading cause of death from infection and a serious complication for patients being treated for other diseases. The threat of lung infections is elevated when there is a decreased level of host resistance (e.g. immunocompromised cancer patients) and when there is an increased level of pathogen exposure (e.g. pandemics, bioterror, and biowarfare). Acute leukemia patients are currently some of the most at-risk patients, as they are faced with significant immunocompromise resulting from their cancer treatments. Many times infectious complications prevent the full cancer treatment plan from being completed. As a result, each year an estimated 44,700 leukemia patients spend more than one-half billion dollars on a range of treatments in an effort to prevent pneumonia. Despite this expenditure, pneumonia continues to occur in 15-20% of acute leukemia patients. Pulmotect's Solution: Pulmotect has identified and is developing a novel, proprietary technology to address the risks of inhaled microbes. Our therapeutic (PUL-042) is a combination of two Toll-like receptor (TLR) agonist ligands that stimulate the lung's own innate defense mechanisms to create a broad protection against invading pathogens thereby reducing and preventing infection. Supported in part by a successful Phase I SBIR, both in vitro and in vivo preclinical proof-of-concept experiments have been completed to validate this technology and further advance it to the clinic. It is in the most at-risk cancer patients where clinical proof-of- concept can be captured and support development for additional patient populations (transplant, ICU, bioterror, pandemic). The focus of this proposal is to accomplish key milestones that will advance this technology further towards commercialization and bridge to funding already secured for Phase I and Phase II clinical trials. The project is organized into four Specific Aims that address the needed data, drug manufacturing, and approvals to bridge this technology to the clinic.